IDENTIFICATION OF HUMAN GENETIC LOCI WHICH INFLUENCE SUSCEPTIBILITY TO HIV

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The clinical course following exposure to HIV is highly variable and this variability is due in part to complex interactions between the host immune system and the virus. Much of the differential response may result from heterogeneity of HIV genomes; however, a reasonable interpretation of the epidemiological data is that host genetic factors influence susceptibility and resistance to both infection and disease outcomes and also contribute to the variable host response to HIV infection observed in human populations. The major objective of this study is to identify those host genetic factors that control infection by the HIV, the immune response to that infection, and host reactivity to the various therapeutics. Immortalized B cell lines are being established from patients in HIV risk groups in collaboration with participating clinical centers with well defined cohorts. The genomic DNA is screened using multiple methods to detect polymorphisms (See Project Z01CP05678-02 LVC). By using a combination of molecular and population genetics, distortions of allelic, genotypic, or linkage equilibrium of linked human loci in clinically defined disease categories, signal that the gene or DNA fragment in disequilibrium may be linked to a locus influencing disease susceptibility or resistance. Approximately 250 restriction fragment length polymorphisms (RFLPs) for both candidate genes and equivalently spaced anonymous RFLPs markers are being used in the screenings. A networked data base to monitor cell and DNA inventory, molecular reagents, accumulated data and genetic analysis has been established.